Tamoxifen for Breast Cancer Risk Reduction
Recruiting in Palo Alto (17 mi)
+10 other locations
Overseen byLisa Barroilhet
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: CYP3A4 inducers, CYP2D6 inhibitors, Warfarin
Disqualifiers: Invasive breast cancer, Bilateral breast surgery, Thromboembolism, others
No Placebo Group
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial evaluates response-guided low-dose tamoxifen for reducing breast density in women who are at higher than average risk for breast cancer. Increasing breast density is a well established risk factor for breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen has been shown to reduce breast density, even at reduced dosages, and is approved for the prevention of breast cancer.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications, specifically strong CYP3A4 inducers or strong CYP2D6 inhibitors, unless you can switch to an alternative medication with your doctor's guidance. If you are currently taking Warfarin, you will not be eligible to participate.
What data supports the effectiveness of the drug Tamoxifen for reducing breast cancer risk?
Research shows that Tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. It is particularly beneficial for women with certain genetic mutations or pre-existing conditions, and it also helps in extending survival and reducing the chance of cancer in the other breast.
12345Is tamoxifen generally safe for humans?
Tamoxifen has been used for many years to treat breast cancer and reduce its risk, but it can have side effects. Some women may experience bone loss, uterine issues like polyps or cancer, and mild side effects. Regular check-ups are recommended to monitor these risks.
12456How is the drug Tamoxifen unique for breast cancer risk reduction?
Tamoxifen is unique because it works by blocking estrogen receptors in breast tissue, which can help reduce the risk of developing breast cancer. This mechanism is different from other treatments that may target cancer cells directly or use different pathways to prevent cancer growth.
7891011Eligibility Criteria
This trial is for premenopausal women at higher than average risk for breast cancer, particularly those with dense breasts. The study aims to find the best dose of Tamoxifen that can reduce breast density and thus lower the risk of developing breast cancer.Inclusion Criteria
I am a woman taking medication to control my HSV infection.
Women of child-bearing potential agreeing to use adequate contraception
Ability to understand and sign a written informed consent document
+8 more
Exclusion Criteria
Receiving any other investigational agents
Uncontrolled intercurrent illness or psychiatric illness/social situations limiting compliance
I have used SERMs for more than a year in the last 5 years.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive tamoxifen 5mg PO QD for 6 months. Dose escalation based on response.
6 months
Monthly visits (in-person)
Dose Escalation
Participants with less than 10% reduction in dense area escalate to 10mg or 20mg tamoxifen.
6-12 months
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
The RENAISSANCE Trial is testing low-dose Tamoxifen's effectiveness in reducing breast density among high-risk women. It includes assessments like questionnaires, biopsies, biospecimen collection, and mammography to monitor changes and responses.
1Treatment groups
Experimental Treatment
Group I: Prevention (tamoxifen)Experimental Treatment5 Interventions
Participants receive tamoxifen 5mg PO QD for 6 months. Participants with aDAR \>= 10% on mammogram at 6 months continue receiving tamoxifen 5mg PO QD for 12 months. Participants with aDAR \< 10% at 6 months are escalated to receive tamoxifen 10mg PO QD for 6 months. Participants with aDAR \>= 10% after 6 months of tamoxifen 10mg continue receiving tamoxifen 10 mg PO QD for 6 months. Participants with aDAR \< 10% after 6 months of tamoxifen 10mg are given the option of continuing tamoxifen 10mg or escalating to receive tamoxifen 20mg PO QD for 6 months. Participants undergo mammography and collection of blood samples at screening and on study. Participants may optionally undergo biopsy at screening and on study.
Tamoxifen is already approved in European Union, United States, Canada, Japan, Australia for the following indications:
🇪🇺 Approved in European Union as Nolvadex for:
- Breast cancer
- Infertility
- Gynecomastia
🇺🇸 Approved in United States as Tamoxifen citrate for:
- Breast cancer
- Reduction in breast cancer incidence in high-risk women
- McCune-Albright Syndrome
🇨🇦 Approved in Canada as Tamoxifen for:
- Breast cancer
- Reduction in breast cancer incidence in high-risk women
🇯🇵 Approved in Japan as Tamoxifen for:
- Breast cancer
🇦🇺 Approved in Australia as Tamoxifen for:
- Breast cancer
- Infertility
- Gynecomastia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Illinois College of Medicine - ChicagoChicago, IL
University of Arizona Cancer Center - Prevention Research ClinicTucson, AZ
University of Kansas Cancer CenterKansas City, KS
Dana-Farber Cancer InstituteBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Tamoxifen's impact on the management of breast cancer: patient perspectives. [2013]Tamoxifen citrate has been prescribed to millions of women with breast cancer and has been one of the most important advances in breast cancer treatment over the past 25 years. Because she is a female physician, the author's patients tend to be particularly open about their concerns regarding breast cancer and its treatment. Women accept tamoxifen as a treatment because of its demonstrated efficacy in breast cancer, extending survival and reducing contralateral breast cancer. They also recognize the potential benefits of secondary effects on lipids and bone. However, patients do have concerns regarding side effects and their impact on everyday life.
Tamoxifen. Use in treatment of metastatic breast cancer refractory to combination chemotherapy. [2019]Tamoxifen citrate (Nolvadex [Great Britain]; no comparable US product) is a recently developed antiestrogen with significant activity against metastatic breast cancer in postmenopausal women. We investigated its usefulness in breast cancer patients after conventional endocrine therapy and combination chemotherapy had failed. Of the 50 evaluable patients, four (8%) achieved a complete remission, 14 (28%) achieved a partial remission, and ten showed a less than partial response or stabilization of their disease. Median duration of response was eight months, and the survival of responders was significantly prolonged compared to that of the nonresponders. Side effects of the treatment were mild. These results demonstrate that tamoxifen offers the best choice of therapy for patients with metastatic breast cancer after conventional endocrine therapy and combination chemotherapy have failed.
Reducing the risk of breast cancer with tamoxifen in women at increased risk. [2013]Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.
Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015]Although tamoxifen citrate has been approved for primary reduction of breast cancer risk since 1998, little is known about the prescription of tamoxifen by primary care physicians.
Status of antiestrogen breast cancer prevention trials. [2016]Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.
The effect of tamoxifen on the endometrium. [2013]Tamoxifen (Nolvadex), a nonsteroidal antiestrogen, was first approved by the FDA for the treatment of patients with breast cancer in 1978. Large clinical trials have demonstrated a recurrence-free and overall survival benefit in both pre- and postmenopausal women. Long-term adjuvant tamoxifen is the endocrine treatment of choice for selected patients with breast cancer, and large-scale trials are currently underway to evaluate its role as a chemopreventive agent in healthy women at risk for breast cancer. Consequently, a large number of women will be subjected to both the benefits and potential risks of long-term tamoxifen therapy. One of the most significant potential complications is the development of endometrial cancer. The estimated annual risk of endometrial cancer in tamoxifen-treated patients is approximately 2 per 1,000 women. Most of these cancers will be detected at an early stage when they are highly curable. The potential benefit of tamoxifen treatment in breast cancer patients outweighs this risk; however, all patients receiving tamoxifen should undergo regular gynecologic evaluations.
Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide. [2021]Leflunomide (LEF) is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA) and the action of which may be modified by sex hormones. The aim of this study was to examine the association between CAG repeat polymorphism in the androgen receptor (AR) gene and the response to treatment with LEF in women with RA.
Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients. [2021]Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). In vitro studies demonstrated that cytochromes P450 (CYPs), mainly CYP1A2 and CYP2C19, might be involved in leflunomide activation. The aim of our study was to investigate whether genetic polymorphisms of CYP1A2, CYP2C19, and CYP2C9 influence leflunomide toxicity.
Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients. [2018]To describe leflunomide (LEF) use in a national cohort of 3,325 veterans.
Genetic polymorphism of CYP1A2 but not total or free teriflunomide concentrations is associated with leflunomide cessation in rheumatoid arthritis. [2021]Leflunomide, via its active metabolite teriflunomide, is used in rheumatoid arthritis (RA) treatment, yet approximately 20 to 40% of patients cease due to toxicity. The aim was to develop a time-to-event model describing leflunomide cessation due to toxicity within a clinical cohort and to investigate potential predictors of cessation such as total and free teriflunomide exposure and pharmacogenetic influences.
Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell carcinoma. [2018]Oral squamous cell carcinoma (OSCC) is the most prevalent pathological cancer occurring in the head and neck area. Progress has previously been made regarding treatment strategies of OSCC, however the 5‑year survival rate of these patients is only 50%. The present study examined if leflunomide (LEF), a drug primarily used for the treatment of rheumatoid arthritis, exhibited antitumor effects in OSCC. The results demonstrated that LEF inhibited cell proliferation and blocked the cell cycle at the S phase in OSCC cells, with upregulation of cyclin A protein expression. LEF reduced the expression of dihydroorotate dehydrogenase, which is an essential enzyme in the de novo pyrimidine biosynthetic pathway. LEF additionally inhibited colony formation in soft agar and reduced tumor growth in a xenograft model. The results suggested that LEF may act as a potential therapeutic agent in the treatment of OSCC in the future.